Adrenocorticotropic hormone (ACTH), prednisone, and vigabatrin (VGB) are first-line treatments for infantile spasms (IS). 1 The antiseizure properties of VGB, an irreversible inhibitor of γ-aminobutyric acid (GABA) transaminase, are thought to emerge from increased levels of GABA. VGB can produce significant adverse effects, including irreversible visual field defects, movement disorders, and vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM). 2,3 VABAM, characterized by diffusion restriction in the globus pallidus, corpus callosum, thalamus, cerebellar dentate nuclei, midbrain, and brainstem, is reported to occur in 22%-32% of IS patients receiving VGB. 4-6 It is dose-dependent, 3 with peak discovery 3-12 months following initiation of VGB. 4,5 It is partially or completely reversed on cessation or dose reduction of VGB. 4-6 Most VABAM are asymptomatic 5 ; however, several case reports describe associated movement disorders (including choreoathetosis, myoclonus, titubation, abnormal eye movements, dystonia, opisthotonos, and tremor), dysautonomia (including bradycardia and respiratory arrest), and acute encephalopathy, together termed symptomatic VABAM. 7-12 In 2017, the International Collaborative Infantile Spasms Study (ICISS), a multicenter, randomized prospective clinical trial, demonstrated increased efficacy of combined hormonal therapy with VGB over hormonal therapy alone for IS. 13 Here, we describe three IS patients who developed symptomatic VABAM when treated contemporaneously with VGB and ACTH, characterized by encephalopathy, dyskinesias, and dysautonomia. A literature review suggests the combination of VGB with hormonal therapy (VGB-HT) is associated with fulminant symptomatic VABAM.